(E)-7-[4-(4-Fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroxyhept-6-enoic acid or a pharmaceutically acceptable salt thereof (rosuvastatin or a salt thereof), especially calcium salt of rosuvastatin (rosuvastatin calcium: monocalcium bis((3R,5S,6E)-7-{4-(4-fluorophenyl)-6-isopropyl-2-[methanesulfonyl(methyl)amino]pyrimidin-5-yl}-3,5-dihydroxyhept-6-enoate))) is described as an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) in European Patent Application No. 0521471 and Bioorganic and Medicinal Chemistry (1997), 5 (2), p. 437-444 and is useful for the treatment of hypercholesterolemia, hyperlipoproteinemia and atherosclerosis.
Rosuvastatin, especially rosuvastatin calcium, is decomposed under given conditions, especially by light or temperature and/or humidity. This makes it difficult to prepare the product into drugs and to obtain a pharmaceutical composition having a favorable storage period.
Examples of literatures of compositions stabilizing rosuvastatin include the following literatures: Patent Document 1 describes a pharmaceutical composition containing rosuvastatin and tribasic phosphate as a stabilizer; Reference 2 describes a pharmaceutical composition containing amorphous rosuvastatin and magnesium hydroxide and/or calcium acetate as a stabilizer; and Reference 3 describes a composition comprising a hypromellose-coated core tablet containing rosuvastatin and a stabilizer. However, even the compositions of these literatures are not sufficiently stabilized against light or temperature and/or humidity.
A dry-coated tablet comprising an inner core tablet containing a drug unstable to light, and an outer layer surrounding the inner core tablet is disclosed as a dosage form protecting a drug unstable to light (References 4 to 6). However, its manufacturing method is very complicated because it is necessary to temporarily manufacture a tablet by tableting the outer layer, and place the inner core tablet on the tablet of the outer layer, followed by compression again. Also, due to the trouble of a tableting machine, the inner core tablet may be displaced from its normal position, or a plurality of inner core tablets may be contained.
In the case of containing drugs unstable to each other, the drugs may be contained in different layers in the form of a multi-layered tablet (References 7 to 9). However, none of these literatures disclose that the preparation can be applied to a drug unstable to light or temperature.
In order to protect a drug unstable to light, a preparation containing the drug may be coated with a light stabilizer, or the preparation may be packaged in aluminum. However, in the former case, the coating of the preparation delays the disintegration the preparation and is thus difficult to apply to a preparation having rapid disintegration, especially an oral disintegrating tablet. Also, in the latter case, there is a possibility that packaging cost is increased, or a packaging step is complicated.